Human recombinant monocyte chemotactic protein and other c-c chemokines bind and induce directional migration of dendritic cells in vitro

Abstract

Because dendritic cells (DC) are the most potent antigen-presenting cells involved in many pathophysiological responses, we investigated the effect of chemokines on the migration of these cells in an effort to determine whether chemokines may contribute to the initiation of immune responses. CD34+ progenitor cells isolated from umbilical cord blood were grown in suspension cultures with cytokines and expanded 50- to 100-fold. A variable proportion of the cells expressed markers consistent with DC. The proportion of CD1a+ DC was increased when the cells were cultured with interleukin-4 (IL-4). These cells expressed specific binding sites for C-C and C-X-C chemokines. Cells cultured with or without IL-4 had similar binding profiles. All C-C chemokines tested, including monocyte chemotactic protein (MCP)-1, MCP-2, MCP-3, macrophage inflammatory protein-1 alpha (MIP1 alpha), MIP-1 beta, and RANTES, induced migration of DC-enriched cells cultured with or without IL-4 with MCP-3 being the most potent chemoattractant. Phenotypic analysis of cell migrating in response to C-C chemokines showed that CD1a+ cells were indeed attracted across the polycarbonate filters, and there was no preferential attraction of contaminating CD14+ monocytes by C-C chemokines. DC-enriched cells also expressed specific binding sites for IL-8 and NAP2, which failed to induce cell migration. Our results suggest that C-C chemokines may participate in the recruitment of DC to amplify host defense.

Role of cytokines in epidermal Langerhans cell migration

“…Responses to chemokines are mediated by chemokine receptors. DC express a variety of chemokine receptors [11,12]. The migratory activity of LC/DC toward chemokines has been investigated by using a chemotaxis microchamber [61,62] or a modified Boyden chamber [63].…”

“…In vitro migration studies using a chemotaxis microchamber or a modified Boyden chamber have demonstrated that a variety of chemokines induce directional migration of DC/LC [11,12]. These chemokines include the CC chemokines, such as macrophage inflammatory protein (MIP)-1␣, MIP-1␤, MIP-5/HCC2, monocyte chemotactic protein (MCP)-1, MCP-2, MCP-3, MCP-4, RANTES (regulated on activation, normal T cell expressed and secreted), macrophage-derived chemokine (MDC), and the CXC chemokine stromal cell-derived factor (SDF)-1 [61][62][63].…”

“…Although it is well known that LC migration is necessary for antigen presentation, little is known about the molecular mechanisms involved. However, research accumulated over the past several years has demonstrated that certain molecules are involved in LC migration: adhesion molecules, including lymphocyte functionassociated antigen-1 (LFA-1)/CD11a, intercellular adhesion molecule-1 (ICAM-1)/CD54, ␣ 6 integrin/CD49f, E-cadherin, and CD44 [5][6][7][8]; cytokines, such as proinflammatory cytokines and chemokines [9][10][11][12]; as well as other molecules including matrix metalloproteinase-9 (MMP-9) and the p-glycoprotein multidrug resistance (MDR)-1 [13][14][15]. Recent studies on gene-targeted knockout mice have further elucidated the role of cytokines and their receptors in the migration of LC.…”

The kinetics of VEGF and MCP-1 in the second vitrectomy cases with proliferative diabetic retinopathy

“…Monocyte chemoattractant protein (MCP)-1 is a small cytokine belonging to the CC chemokine family that recruits monocytes, memory T cells, and dendritic cells to sites of tissue injury, infection, and inflammation. 6,7 It is also induced by hypoxia and bleeding. [8][9][10][11] Clinical studies revealed that MCP-1 increased in the vitreous of patients with PDR and it was suspected of contributing to the progression of diabetic retinopathy.…”

Possible impact of ADRB3 Trp64Arg polymorphism on BMI in patients with schizophrenia

“…Adipocytes also secrete chemokines, particularly monocyte chemoattractant protein 1 (MCP-1). MCP-1 attracts leukocytes such as monocytes, T lymphocytes, and dendritic cells (Carr et al , 1994, Xu et al , 1996, which then secrete inflammatory cytokines such as interleukin-1 (IL-1), IL-6 and tumor necrosis factor-α. MCP-1 is also known to play a critical role in the development of cardiovascular disease and obesity-induced insulin resistance (Niu and Kolattukudy, 2009).…”